Walter C. Low, HD Researcher
The 3-Nitropropionic Acid (3NPA) rat Model of Huntington's Disease is a low cost replacement for the HD mice carrying the human expanded gene. Therapies that work with one model have worked with both models and will most likely work with humans. --Jerry 28-Sep-01
Adapted from:Exp Neurol 2001 Oct;171(2):351-60 Low WC. et al. University of Minnesota Medical School
Walter C. Low, HD Researcher |
It is well established that HD is associated with perturbation of mitochondrial energy metabolism.
Tauroursodeoxycholic acid (TUDCA), a naturally occurring bile acid, can stabilize the mitochondrial membrane, inhibit the mitochondrial permeability transition, decrease free radical formation, and derail apoptotic pathways.
Here we report that TUDCA significantly reduced 3-nitropropionic acid (3-NP)-mediated striatal neuronal cell death in cell culture. In addition, rats treated with TUDCA exhibited an 80% reduction in apoptosis and in lesion volumes associated with 3-NP administration. Moreover, rats which received a combination of TUDCA + 3-NP exhibited sensorimotor and cognitive task performance that was indistinguishable from that of controls, and this effect persisted at least 6 months. Bile acids have traditionally been used as therapeutic agents for certain liver diseases.
This is the first demonstration, however, that a bile acid can be delivered to the brain and function as a neuroprotectant and thus may offer potential therapeutic benefit in the treatment of certain neurodegenerative diseases.